Low-calorie diets for people with isolated impaired fasting glucose

Standard lifestyle interventions prove ineffective in preventing type 2 diabetes among individuals with isolated impaired fasting glucose, a highly prevalent prediabetes phenotype globally. Here, we propose low-calorie diets as a promising strategy for diabetes prevention in this high-risk population.

In recent years, low-calorie diets ranging from 800-1500 kcal/day have gained significant attention in managing type 2 diabetes 8,[16][17][18][19] .Studies have shown that low-calorie diets can lead to remission and substantial improvements in cardiometabolic risk factors for a significant proportion of individuals with type 2 diabetes 8,[16][17][18][19] .These diets are generally well-tolerated and safe, with only mild side effects reported.Table 1 summarizes the key low-calorie diet studies conducted in people with type 2 diabetes 8,[16][17][18][19] .Studies implementing low-calorie diets over a 2-5 month period, primarily high in protein and low in fat, have resulted in a mean weight loss of 7-15 kg (8-15% of initial body weight).This level of weight loss was accompanied by a notable reduction in hepatic fat and improved hepatic insulin sensitivity and first-phase insulin secretion.As a result, fasting plasma glucose levels decreased significantly by 27.8 to 43.2 mg/dL.This suggests that low-calorie diets may also be effective for individuals with i-IFG, as they target the pathophysiological defects characterizing this prediabetes phenotype 8,[16][17][18][19] .Figure 1 visually depicts the potential reversal of the twin cycle hypothesis through low-calorie diets in individuals with i-IFG.The twin cycle hypothesis 20 postulates that chronic excess calorie intake results in increased accumulation of fat in the liver, leading to resistance against insulin's suppression of hepatic glucose production.Additionally, excess liver fat increases lipid transportation to the pancreas, impairing β-cell function and further promoting hepatic glucose production.These self-reinforcing cycles between the liver and pancreas ultimately result in the onset of hyperglycemia.
The assertion that low-calorie diets could potentially reverse the twin cycle hypothesis in i-IFG is supported by a post-hoc analysis of the PRE-VIEW (PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World) study, involving 869 individuals (mean age 55.0 years) with overweight (body mass index ≥25 kg/ m 2 ) and i-IFG 21 .Following an 8-week low-calorie diet phase (810 kcal/day; 41.2% carbohydrate, 43.7% protein, 15.1% fat), the mean weight loss was 10.8 kg (10.7%), with more than four-fifths (82.7%) of participants achieving the targeted weight loss of ≥8%.Notably, the weight loss led to a reduction in mean fasting plasma glucose of 6.5 mg/dl, with slightly over one-third (36.1%) achieving normoglycemia based on fasting plasma glucose alone 21 .The hepatic insulin resistance index significantly decreased by 30%, from 76.69 (SD: 2.31) to 47.42 (SD: 2.41), p < 0.001.communications medicine

Comment
Current diabetes prevention guidelines fail to recognize the heterogeneity of prediabetes [22][23][24] concerning differences in pathophysiological abnormalities 2,3 and progression rates to type 2 diabetes among its phenotypes 9 .These guidelines inform the design and development of national diabetes prevention programs that typically deliver standard lifestyle interventions to individuals with any prediabetes phenotype [25][26][27] .However, recent evidence suggests that standard lifestyle interventions prove ineffective for individuals with i-IFG, while they remain highly effective for those with IGT (with or without IFG) in reducing diabetes incidence 12,28,29 .Therefore, there is an urgent need for further research to identify lifestyle modification strategies tailored specifically to address the distinct pathophysiological defects associated with i-IFG, including investigating the potential efficacy of low-calorie diets.

Fig. 1 |
Fig. 1 | Potential reversal of the twin cycle hypothesis through low-calorie diets in isolated impaired fasting glucose.VLDL very low density lipoprotein.

Table 1 |
Summary of key low-calorie diet studies in people with type 2 diabetesDiRECT Diabetes Remission Clinical Trial, BMI body mass index, RCT randomized controlled trial, LCD low-calorie diet, FPG fasting plasma glucose, SD standard deviation, CI confidence interval, QUICKI quantitative insulin-sensitivity check index.